In a new study in experimental models and humans, researchers at the University of Western Ontario, Canada, have shown that female sex hormones play a significant role in how Alzheimer’s manifests in the brain.

Alzheimer’s disease disproportionately affects women, who represent about two-thirds of those diagnosed with the late-onset type of the disease. The biological bases for these differences between men and women with Alzheimer’s disease are not well understood. However, understanding them is necessary for developing appropriate therapies.

The study, published in the journal Alzheimer's & Dementia, also highlights the importance of developing therapeutic strategies focused on these hormonal connections.

The research indicates a need to better understand the role of estradiol a form of the female sex hormone estrogen, used therapeutically to mitigate menopause symptoms in Alzheimer’s disease.

“To understand how sex hormones play a role in Alzheimer’s, we need to study appropriate experimental models. Unfortunately, most studies at this level still focus mainly on the male brain,” said Vania Prado, professor, of the departments of physiology and pharmacology and anatomy & cell biology at Schulich School of Medicine & Dentistry.

Our research emphasises the importance of using experimental models that reflect, for instance, postmenopausal women, to understand how sex hormones influence Alzheimer’s pathology, Prado added.

One of the key markers of Alzheimer’s disease is the toxic build-up of the protein beta-amyloid in the brain, which eventually disrupts the brain’s communications system and impacts cognition.

The new study shows that the brain chemistry of male and female experimental models regulates beta-amyloid protein in Alzheimer’s in different ways, with the hormone estradiol contributing to this variation.

“We found that when the sex hormone estradiol was present, the relationship between acetylcholine and toxic amyloid was lost, but when sex hormones were eliminated in the female experimental models that relationship reproduced the results seen in humans,” said study leader Liliana German-Castelan.

Researchers emphasised that if they hadn't included female experimental models in the study, they might have missed crucial information about Alzheimer's and sex differences.

“To develop more effective therapeutics, we need to study experimental models that can reproduce different aspects of the journey. Sex hormones and estradiol levels are just one of these factors,” said Prado.